Fibrinogen matrix enhances biodistribution of induced pluripotent stem cells for cellular cardiomyoplasty in ischemic heart failure

2011 ◽  
Vol 59 (S 01) ◽  
Author(s):  
SV Rojas ◽  
A Martens ◽  
H Baraki ◽  
C Rathert ◽  
N Schecker ◽  
...  
2016 ◽  
Vol 41 (2) ◽  
pp. 192-199 ◽  
Author(s):  
Sebastian V. Rojas ◽  
Martin Meier ◽  
Robert Zweigerdt ◽  
Dominik Eckardt ◽  
Christian Rathert ◽  
...  

Author(s):  
Chrishan J A Ramachandra ◽  
Jasper Chua ◽  
Shuo Cong ◽  
Myu Mai Ja Kp ◽  
Winston Shim ◽  
...  

Abstract Normal cardiac contractile and relaxation functions are critically dependent on a continuous energy supply. Accordingly, metabolic perturbations and impaired mitochondrial bioenergetics with subsequent disruption of ATP production underpin a wide variety of cardiac diseases, including diabetic cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, anthracycline cardiomyopathy, peripartum cardiomyopathy, and mitochondrial cardiomyopathies. Crucially, there are no specific treatments for preventing the onset or progression of these cardiomyopathies to heart failure, one of the leading causes of death and disability worldwide. Therefore, new treatments are needed to target the metabolic disturbances and impaired mitochondrial bioenergetics underlying these cardiomyopathies in order to improve health outcomes in these patients. However, investigation of the underlying mechanisms and the identification of novel therapeutic targets have been hampered by the lack of appropriate animal disease models. Furthermore, interspecies variation precludes the use of animal models for studying certain disorders, whereas patient-derived primary cell lines have limited lifespan and availability. Fortunately, the discovery of human-induced pluripotent stem cells has provided a promising tool for modelling cardiomyopathies via human heart tissue in a dish. In this review article, we highlight the use of patient-derived iPSCs for studying the pathogenesis underlying cardiomyopathies associated with metabolic perturbations and impaired mitochondrial bioenergetics, as the ability of iPSCs for self-renewal and differentiation makes them an ideal platform for investigating disease pathogenesis in a controlled in vitro environment. Continuing progress will help elucidate novel mechanistic pathways, and discover novel therapies for preventing the onset and progression of heart failure, thereby advancing a new era of personalized therapeutics for improving health outcomes in patients with cardiomyopathy.


Author(s):  
Anton Deicher ◽  
Timon Seeger

Abstract Purpose of Review Heart failure is among the most prevalent disease complexes overall and is associated with high morbidity and mortality. The underlying aetiology is manifold including coronary artery disease, genetic alterations and mutations, viral infections, adverse immune responses, and cardiac toxicity. To date, no specific therapies have been developed despite notable efforts. This can especially be attributed to hurdles in translational research, mainly due to the lack of proficient models of heart failure limited translation of therapeutic approaches from bench to bedside. Recent Findings Human induced pluripotent stem cells (hiPSCs) are rising in popularity, granting the ability to divide infinitely, to hold human, patient-specific genome, and to differentiate into any human cell, including cardiomyocytes (hiPSC-CMs). This brings magnificent promise to cardiological research, providing the possibility to recapitulate cardiac diseases in a dish. Advances in yield, maturity, and in vivo resemblance due to straightforward, low-cost protocols, high-throughput approaches, and complex 3D cultures have made this tool widely applicable. In recent years, hiPSC-CMs have been used to model a wide variety of cardiac diseases, bringing along the possibility to not only elucidate molecular mechanisms but also to test novel therapeutic approaches in the dish. Summary Within the last decade, hiPSC-CMs have been exponentially employed to model heart failure. Constant advancements are aiming at improvements of differentiation protocols, hiPSC-CM maturity, and assays to elucidate molecular mechanisms and cellular functions. However, hiPSC-CMs are remaining relatively immature, and in vitro models can only partially recapitulate the complex interactions in vivo. Nevertheless, hiPSC-CMs have evolved as an essential model system in cardiovascular research.


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